{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:33:10Z","timestamp":1780054390372,"version":"3.54.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471650"],"award-info":[{"award-number":["82471650"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2706402"],"award-info":[{"award-number":["2023YFC2706402"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Tdrd12<\/jats:italic>\n                    is known to play an important role in spermatogenesis in mice. However, evidence linking\n                    <jats:italic>TDRD12<\/jats:italic>\n                    mutations to male azoospermia is limited, and no cases of\n                    <jats:italic>TDRD12<\/jats:italic>\n                    \u2010related teratozoospermia have been reported. We identified two novel homozygous\n                    <jats:italic>TDRD12<\/jats:italic>\n                    mutations (c.3378dupG and c.2463C&gt;G) in two unrelated infertile men, respectively. Patient 1 carried a\n                    <jats:italic>TDRD12<\/jats:italic>\n                    frameshift mutation (c.3378dupG), resulting in a truncated protein lacking the cysteine\u2010rich domain. This patient presented with teratozoospermia, characterized by abnormal sperm morphology, including defects in the head and flagellum. Patient 2 carried a\n                    <jats:italic>TDRD12<\/jats:italic>\n                    nonsense mutation (c.2463C&gt;G), resulting in complete degradation of the protein. This patient exhibited azoospermia, characterized by germ cell maturation arrest at the spermatocyte stage. Mechanistically, TDRKH, TDRD9, PIWIL2, and PIWIL1, key piRNA biogenesis proteins, are predicted to interact with TDRD12. Notably, PIWIL1 fluorescence was reduced in Patient 1's sperm, while PIWIL2 and TDRD9 signals were diminished and LINE\u20101 signal was increased in Patient 2's testicular tissue. Furthermore, Intracytoplasmic sperm injection using Patient 1's sperm was unsuccessful. Our study first identified that the loss of different domains of TDRD12 results in distinct male infertility\u2010related phenotypes. These findings revealed novel genetic insights into male infertility, demonstrated the critical role of\n                    <jats:italic>TDRD12<\/jats:italic>\n                    in human spermatogenesis, and are helpful for diagnosis and genetic counseling.\n                  <\/jats:p>","DOI":"10.1111\/cge.70034","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T01:09:37Z","timestamp":1754096977000},"page":"255-265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of Different Domains of\n                    <scp>TDRD12<\/scp>\n                    Leads to Distinct Male Infertility\u2010Related Phenotypes"],"prefix":"10.1111","volume":"109","author":[{"given":"Xinyao","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education West China Second University Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanjuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Reproduction Medical Center of West China Second University Hospital, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Sichuan University  Chengdu China"},{"name":"Tianfu Jincheng Laboratory City of Future Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8930-6801","authenticated-orcid":false,"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingteng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiechao","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education West China Second University Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guicheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Reproduction Medical Center of West China Second University Hospital, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproduction Medical Center of West China Second University Hospital, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-015-0032-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00459-w"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmaa034"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32667-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-023-00816-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.087"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-169X.2011.01320.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.5713\/ajas.15.0436"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316316110"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1814809"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061127"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.240895.114"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp048"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911640106"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwu014"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2019.1603199"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601878103"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.10.012"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50930-9"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-104514"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201009043"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46664-3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015447108"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.130"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.03.040"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2024.06.014"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(98)90035-0"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.022"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10547"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10672"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.121"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70034","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70034","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:42:09Z","timestamp":1776645729000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/cge.70034"],"URL":"https:\/\/doi.org\/10.1111\/cge.70034","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,1]]},"assertion":[{"value":"2025-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}